Improved accumulation of ajmalicine and tetrahydroalstonine in Catharanthus cells expressing an ABC transporter

Pomahačová, Barbora; Dušek, Jaromír; Duskova, J.; Yazaki, Kazufumi; Roytrakul, Sittiruk; Verpoorte, Robert

doi:10.1016/j.jplph.2009.02.015

Cited by 22 publications

(8 citation statements)

References 48 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A series of genes encoding MIA biosynthetic enzymes (anthranilate synthase alpha subunit, Asα; 1-deoxy-D-xylulose synthase, DXS; tryptophan decarboxylase, TDC; strictosidine synthase, STR; strictosidine beta-glucosidase, SGD; geraniol 10-hydroxylase, G10H; desacetoxyvindoline 4-hydroxylase, DAT; apoplastic peroxidase, CrPrx; secologanin synthase, SLS) have been characterized, cloned and overexpressed alone or in combination in cell cultures and hairy roots of C. roseus in the past decade [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]. Transformation of transcription factors (ORCA2 and ORCA3) [16], transporters (ATP-binding cassette transporter, ABC) [17] and heterologous genes (Bcl-2 Associated X protein, Bax) [18] were also performed in C. roseus cells and hairy roos. Genetic modification is a good approach to study the regulation of MIA biosynthesis and to improve the production of targeted MIAs in C. roseus , thus lower the production costs for these very expensive clinical medicines.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of ORCA3 and G10H in Catharanthus roseus Plants Regulated Alkaloid Biosynthesis and Metabolism Revealed by NMR-Metabolomics

et al. 2012

Self Cite

View full text Add to dashboard Cite

In order to improve the production of the anticancer dimeric indole alkaloids in Catharanthuse roseus, much research has been dedicated to culturing cell lines, hairy roots, and efforts to elucidate the regulation of the monoterpenoid indole alkaloid (MIA) biosynthesis. In this study, the ORCA3 (Octadecanoid-derivative Responsive Catharanthus AP2-domain) gene alone or integrated with the G10H (geraniol 10-hydroxylase) gene were first introduced into C. roseus plants. Transgenic C. roseus plants overexpressing ORCA3 alone (OR lines), or co-overexpressing G10H and ORCA3 (GO lines) were obtained by genetic modification. ORCA3 overexpression induced an increase of AS, TDC, STR and D4H transcripts but did not affect CRMYC2 and G10H transcription. G10H transcripts showed a significant increase under G10H and ORCA3 co-overexpression. ORCA3 and G10H overexpression significantly increased the accumulation of strictosidine, vindoline, catharanthine and ajmalicine but had limited effects on anhydrovinblastine and vinblastine levels. NMR-based metabolomics confirmed the higher accumulation of monomeric indole alkaloids in OR and GO lines. Multivariate data analysis of 1H NMR spectra showed change of amino acid, organic acid, sugar and phenylpropanoid levels in both OR and GO lines compared to the controls. The result indicated that enhancement of MIA biosynthesis by ORCA3 and G10H overexpression might affect other metabolic pathways in the plant metabolism of C. roseus.

show abstract

Section: Introductionmentioning

confidence: 99%

Overexpression of ORCA3 and G10H in Catharanthus roseus Plants Regulated Alkaloid Biosynthesis and Metabolism Revealed by NMR-Metabolomics

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, MAP kinases (including ERK, JNK, and p38) are known to be involved in the regulation of MMP-9 transcription (20). However, previous reports showed that TPA-induced MMP-9 expression is inhibited by the MEK1/2 inhibitor, but not by JNK and p38 inhibitors, in MCF-7 cells (3,4,18). Similar to these reports, the present study showed that CR4-1 effectively suppressed TPA-induced MMP-9 gene expression by reducing ERK (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…C. roseus is known to exert effective cancer preventive and therapeutic effects through inhibition of cell viabiliity, cell cycle progression, and apoptosis in various cancer cell lines (3,18,19). However, the mechanism underlying the inhibitory effects of CR4-1 on tumor metastasis and angiogenesis in breast cancer has not been completely elucidated.…”

Section: Discussionmentioning

confidence: 99%

The Cadin-2-en-1β-ol-1β-D-glucuronopyranoside Suppresses TPA-Mediated Matrix Metalloproteinase-9 Expression Through the ERK Signaling Pathway in MCF-7 Human Breast Adenocarcinoma Cells

Kim

Bak

et al. 2012

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract.A sesquiterpene glycoside, cadin-2-en-1β-ol-1β-D-glucuronopyranoside (known as CR4-1), was isolated from Catharanthus roseus (Apocynaceae) hairy root cultures. C. roseus is widely used as an ornamental and medicinal plant and is cultivated mainly for its alkaloids. C. roseus has been reported to have pharmacologic properties such as anti-cancer, enzymatic antioxidant, and anti-diabetic effects. In this study, we demonstrated that CR4-1 significantly inhibited the in vitro invasion of MCF-7 human breast adenocarcinoma cells induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Matrix metalloproteinases (MMPs) are known to be involved in cancer invasion and metastasis. Zymographic analysis showed that CR4-1 suppressed TPA-induced MMP-9 activity in a dose-dependent manner. We further demonstrated that CR4-1 suppressed the phosphorylation of extracellular signal-regulated protein kinase, but not p38 kinase or c-Jun Nterminal kinase (JNK). Moreover, CR4-1 attenuated TPA-induced degradation of κBα inhibitor (IκB-α). These results suggest that CR4-1 reduces the invasiveness of human cancer cells by suppressing MMP-9 expression through inhibition of the NF-κB signaling pathways.

show abstract

“…Overexpression of CjABCB1 in the cultured cells of C. roseus (Madagascar periwinkle), which does not produce berberine, but does biosynthesize monoterpenoid indole alkaloids (MIAs), significantly increased the accumulation of the MIAs ajmalicine and tetrahydroalstonine, when the cells were fed with these alkaloids. These MIAs might be recognized by CjABCB1 and transported into C. roseus cells (Pomahacova et al 2009). …”

Section: Berberine Transport In Coptis Japonicamentioning

confidence: 99%

“…As shown for CjABCB1, CrTPT2 and NtNUP1, altering the expression of alkaloid transporters influences the accumulation, and sometimes also the production, of relevant alkaloids (Hildreth et al 2011;Pomahacova et al 2009;Shitan et al 2005;Yu and De Luca 2013). However, the mechanistic details underlying these phenomena remain unclear.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Alkaloid transporters in plants

Shitan

Kato

Shoji

2014

Plant Biotechnology

View full text Add to dashboard Cite

Plants produce a multitude of secondary metabolites, including alkaloids with biological activities, and many alkaloids have been used for medicinal purposes. The biosynthetic enzymes and genes involved in alkaloid metabolic pathways exhibit divergent localizations, implying that alkaloid metabolites, including pathway products and intermediates, travel from organelle to organelle, cell to cell, and organ to organ. Biochemical studies have indicated that specific transporters move these metabolites. Indeed, molecular and cellular approaches have identified alkaloid transporters of the ATP-binding cassette (ABC) protein, multidrug and toxic compound extrusion (MATE), and purine permease (PUP) families. Interestingly, some of these transporters were found to be required for the efficient biosynthesis of alkaloids in plants. Here, we provide an updated inventory of alkaloid transporters and discuss the possibility of genetically manipulating the expression of these transporters to increase the accumulation of valuable alkaloid compounds.

show abstract

Improved accumulation of ajmalicine and tetrahydroalstonine in Catharanthus cells expressing an ABC transporter

Cited by 22 publications

References 48 publications

Overexpression of ORCA3 and G10H in Catharanthus roseus Plants Regulated Alkaloid Biosynthesis and Metabolism Revealed by NMR-Metabolomics

Overexpression of ORCA3 and G10H in Catharanthus roseus Plants Regulated Alkaloid Biosynthesis and Metabolism Revealed by NMR-Metabolomics

The Cadin-2-en-1β-ol-1β-D-glucuronopyranoside Suppresses TPA-Mediated Matrix Metalloproteinase-9 Expression Through the ERK Signaling Pathway in MCF-7 Human Breast Adenocarcinoma Cells

Alkaloid transporters in plants

Contact Info

Product

Resources

About